Seminar

Structural Biology of Genome Editing: How RNA-guided endonucleases cut specific regions of the Genome?

Prof. Guillermo Montoya

Since ancestral time mankind has tried to modify plants and animals to obtain an offspring that could adapt to our needs. In this way farmers have selected more efficient animals to produce more meat, more resistant plants, faster and resistant horses or cows that produce a larger amount of milk. Our ability to modify organisms has changed dramatically with the introduction of genome editing, til a point where we can start to redesign an organism. Thanks to the discovery of new genome modifying enzymes we can perform a safer and faster manipulation to edit a genome. I will address the molecular mechanism that control specificity and cleavage of one of these tools, Cpf1, a single RNA-guided endonuclease of class 2 type V CRISPR-Cas system, which is emerging as a powerful genome editing tool. To provide insight into its DNA targeting mechanism, we have determined the crystal structure of Francisella novicida Cpf1(FnCpf1) in complex with the triple strand R-loop formed after target DNA cleavage. The structure reveals a unique machinery for target DNA unwinding to form a crRNA-DNA hybrid and a displaced DNA strand inside FnCpf1. Our study reveals a singular working model of RNA-guided DNA cleavage by Cpf1, opening up new avenues for engineering this genome modification system.